DESCRIPTION: In this proposal a specific neuroendocrine pathway has been chosen to examine the determinants of individual variation in the structure and function of the brain. This is a complex pathway which determines the photoperiodic response and which finally affects the reproductive responsiveness. The model to be used is the natural population of the white footed mouse (Peromyocus leucopus) because in this genus the photoresponsive pathway contains wide genetic variation in this trait ranging from reproductive suppression to an almost complete lack of response to photoperiod. The mice will be artificially-selected by raising the mice in the laboratory under long and short photo periods, thus obtaining responsive and unresponsive lines. Differences between selected lines of mice at variable points in the neuroendocrine pathway linking photoperiod to the reproductive axis will be determined. The information will be used to develop a testable model for the evaluation of neuroendocrine pathways. The first aim will determine the amount and genetics of variation in reproductive photo responsiveness by measuring testicular size or ovarian and uterine size of animals exposed to long or short photo periods. In Aim 2 the neuroanatomical nature of photoresponsiveness will be determined by examining the variation in GnRH neurons using immunocytochemistry, variation in response to melatonin, variation in dopaminergic pathways and variation in response of GnRH neurons to excitatory amino acids. The third aim will provide a predictive and testable model for individual variation based on the information obtained in the numerous experiments of the previous aims.